1. Field of Invention
The present invention relates to preparation of the (+) or (R)-enantiomer of an RAR.gamma.-specific agonist previously described in the prior art and the discovery that all of the retinoid activity of such agonist resided in such enantiomer.
The (R)-enantiomer of the present invention may be used in a wide variety of dermatological conditions, e.g. acne, psoriasis, eczema and photoaging of the skin, in treatment of corneopathies in opthamology, in treatment of degenerative diseases of connective tissue, e.g. arthritis, and in the treatment of malignancies.
2. Description of the Prior Art
U.S. Pat. No. 5,624,957 discloses the racemic compound, 3-fluoro-4(2'(5",6",7",8"-tetrahydro-5",5",8",8"-tetramethyl-2"-naphthyl)- 2'-hydroxy)acetamidobenzoic acid (see Example 1) as an RAR.gamma.-specific retinoid with the highly useful property of lacking the liver toxicity of non-elective retinoids. The compound is also disclosed by B. P. Klaholz, et al., Nature Structural Biology, 5(3), pp. 199-202 (1998), as a complex with the RAR.gamma. receptor protein. However, the compound indicated as binding to the receptor is the (S)-enantiomer, which is the inactive form.
Although the above-described patent reference indicates that the disclosed RAR.gamma.-specific retinoids exist in the form of the individual enantiomers as well as racemic mixtures, there is no disclosure of the (R)-enantiomer or the fact that, unexpectedly, all of the retinoid activity of the compound of Example 1 resides in this enantiomer.